Quality of life measures in health care. III: Resource allocation.
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Biomedical subjects
Publications and source records attributed to D R Jones.
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Systemic lupus erythematosus (SLE) occurs in human beings and in dogs. There is evidence to suggest that the disease is caused by a transmissible factor that may cross the species barrier. We investigated this possibility by looking for autoantibodies and serum protein abnormalities in serum samples from 15 pet dogs owned by patients with SLE and comparing results with those obtained with serum from 10 healthy dogs kept in a controlled environment and 9 dogs with autoimmune diseases. We used standard immunological assays modified for use with canine samples. Compared with the normal dogs, increased amounts of antibody to double-stranded DNA were found in serum from the SLE patients' dogs (median optical density [405 nm] = 0.117 vs 0.299; p = 0.0001), this latter amount being similar to that found in serum from the autoimmune group (0.201; p = 0.6). Abnormal serum protein electrophoresis patterns were found in samples from the autoimmune and SLE patients' dogs but not the normal dogs. These findings support the idea that exposure to common environmental factors or transmissible agents may have a role in causing SLE.
POSSUM and APACHE II scores from 117 consecutive admissions to a high-dependency unit after major surgery were correlated with 30-day morbidity and mortality rates. Thirteen patients (11 per cent) died and 59 (50 per cent) developed a postoperative complication. Receiver-operating characteristic curve analysis showed POSSUM to have good predictive value for mortality (area under curve 0.75) and morbidity (area under curve 0.82). APACHE II scores had a significantly inferior predictive value for mortality (area under curve 0.54) (P < 0.002). POSSUM was superior to APACHE II in prediction of mortality in patients admitted to a high-dependency unit after general surgery. Prediction of postoperative complications by POSSUM is accurate and may be useful for audit.
To explore the potential for structural variation and new growth at the synapse, we studied the morphological patterns of the end-bulbs of cochlear nerve axons in adult cats by using rapid Golgi, reduced silver, and electron microscopic methods. Horseradish peroxidase labeling of these endings in the anterior division of the antroventral cochlear nucleus was produced by anterograde transport following injection into the cochlea. Three types of end-bulbs were distinguished, regardless of method: reticular, coalescent, and ringed forms, all synapsing on spherical bushy cells. The reticular variety corresponds to the classically described end-bulb and constitutes the majority in all regions of the tonotopic map. The ringed end-bulb, described here for the first time, forms an excitatory synaptic cuff around the base of a bushy cell's main dendrite; these endings were localized to the region receiving cochlear input in the 1-6 kHz range, which is used in vocalization. The coalescent ending forms a small fraction of the end-bulb population throughout the region studied. The findings raise the possibility of functional differences between these synaptic types. Growth cones and retraction clubs were present on most, if not all, of the end-bulbs in every adult cat studied. A systematic survey of the end-bulb patterns revealed a continuous gradient of variation, in which each synaptic type forms a distinct mode. These findings lead us to hypothesize that the end-bulbs are in a continual state of structural and functional flux. These endings should prove useful for studies on the modifiable properties of central synapses.
Roles of statisticians in drug regulatory agencies include assessment of the adequacy of statistical aspects of the design of the programme of efficacy and safety studies, design of individual studies, data collection and quality assurance in each study, analysis of individual studies, interpretation of individual studies, and interpretation of results of the programme. These assessments should be made in collaboration with medical, pharmacological, and toxicological colleagues, and liaison with company statisticians before, during, and after submission of the application if the procedure is to be efficient. Recommendations for improving statistical quality of drug license applications and provision for their statistical review in Europe include: 1. Employment of more experienced, professional statistical assessors in both national and European Community (EC) regulatory authorities, with a wider group of supporting experts 2. Obligatory statistical coauthorship or validation of expert reports before submission of applications, and 3. Unified statistical guidelines for preparation of applications.
The dynamic role of arterial baroreceptors in control of mean arterial blood pressure (MAP), heart rate (HR), cardiac output (CO), hindlimb vascular (HLVR) and total peripheral (TPR) resistance responses to forced dives was investigated in acutely and chronically barodenervated ducks. To activate the baroreflex, the proximal end of one aortic nerve was stimulated electrically with bipolar electrodes that had been implanted under pentobarbital sodium anesthesia. Predive nerve stimulation caused CO to fall (by reducing HR; stroke volume remained constant), producing a decrease in MAP to half the prestimulation level. During diving (for 2.5-min periods) nerve stimulation did not affect HR and MAP after the first minute of submersion. Neither HLVR nor TPR contributed to the fall in MAP during aortic nerve stimulation before or during diving. The effects of nerve stimulation on HR and MAP were maintained to the end of dives in animals given 100% O2 to breathe before diving. In separate experiments, increasing arterial chemoreceptor input by perfusing one vascularly isolated carotid body with venous blood caused a reduction in the effects of aortic nerve stimulation on MAP. Arterial baroreceptors may thus act on HR to alter MAP early in the dive, but as the dive progresses the baroreflex is attenuated by an increase in peripheral chemoreceptor drive.
We tested the hypothesis that forced-dived ducks experience a reduction in metabolic rate during prolonged submergence. Unidirectionally ventilated conscious ducks were subjected to forced dives by temporarily stopping the airflow in the ventilation system and simultaneously filling a face mask with cold water. A typical cardiovascular response to submergence was observed: bradycardia and maintained arterial blood pressure. Phosphorylated metabolite concentrations in the pectoral muscle were measured noninvasively by phosphorus magnetic resonance spectroscopy (31P-MRS). ATP content was constant, and phosphocreatine was depleted via the creatine kinase reaction at a rate similar to the resting rate of ATP turnover, which was estimated to be 0.9 mumol.min-1 x g-1 in resting perfused pectoral muscle of pentobarbital-anesthetized ducks. Oxygen from myoglobin supplied at most 12% of the ATP required by the resting muscle during dives. Whole animal postdive excess oxygen consumption and blood lactic acid accumulation suggested that the shortfall in aerobic metabolism during forced dives was compensated by an increase in anaerobic metabolism.
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Sensory neocortex of the tree shrew was divided into three main areas: the visual field, the auditory field, and the somatic field which includes motor cortex. Cortical cells which project to the tectum were identified by injecting HRP into superficial or deep layers of the superior colliculus and into various parts of the inferior colliculus. The main result is that these descending projections are well organized according to their origin in the three main sensory fields of the cortex. (1) Auditory field: labeled cells are found only in the core or auditory koniocortex, after injections of HRP in the pericentral area of the inferior colliculus; labeled cells are found in auditory belt areas after injections in posterior parts of the intermediate and deep layers of the superior colliculus, adjacent to the inferior colliculus. (2) Somatic field: labeled cells are also found in the somatic field after injections in the intermediate and deep layers of the superior colliculus, so that auditory and somatic fields probably overlap to some extent. The results do not exclude the possibility that somatic koniocortex has an exclusive target in the intermediate or deep layers of the superior colliculus. (3) Visual field: labeled cells are found only in the core or striate cortex after injections in the superficial layers of the superior colliculus. Labeled cells are found in the visual belt after injections in the rostral parts of the intermediate layers of the superior colliculus. When these results are related to ascending sensory pathways a picture emerges of a series of circuits or loops which interconnect parallel sensory pathways. These loops eventually reach the deep layers of the superior colliculus which of course have indirect access to motor neurons.
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Use of a computer simulation technique as a tool for optimising the design of a clinical trial is described. One of several aspects of trial design facilitated by use of the technique is the estimation of the number of patients required in the trial. The simulation tool provides the basis for structured and disciplined discussion of all the issues to be considered in designing a trial. Copies of the simulation program are available from the author.
Ventilatory responses of unanesthetized turtles to changes in the intrapulmonary CO2 content of a vascularly isolated and an intact lung were measured during spontaneous breathing. The hyperpnea associated with inhalation of CO2 by the vascularly isolated lung was 19% of that associated with inhalation of CO2 by the intact lung. Transection of the vagus nerve supplying the isolated lung abolished this response. We conclude that both inhibition of pulmonary stretch receptor discharge with increasing levels of FICO2 and a functional increase in central inspiratory volume threshold during hypercapnia contribute to tidal volume increases following CO2 inhalation in normal animals. The major component of the ventilatory response of intact turtles to increasing levels of FICO2, however, was an increase in respiratory frequency. When CO2 was inspired only by the vascularly isolated lung the increase in respiratory frequency was only 21% of that recorded when the same levels of CO2 were inspired by the intact lung. Thus the ventilatory response of turtles to increasing levels of FICO2 is primarily dependent upon concomitant hypercapnia.
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This study was of the role of admissions committees as it relates to the mental health of applicants. Two-part questionnaires were sent to 115 medical schools. The first part explored the composition of the committee. In most schools the dean selected the members, attempting to obtain equal representation from clinical and basic science departments; most of the schools had one or more psychiatrists on the committee. The second part focused on the policy for applicants with former mental health problems. Over one-third of the committees asked about previous or present mental illness or therapy. Ninety percent of the schools had no policy or guidelines for using such information; instead, most relied on psychiatric interview or outside reports in making admissions decisions. The impact of federal legislation regarding the handicapped on admissions procedures is discussed. Since more students with previous or current psychiatric problems may be admitted, schools must be prepared to respond to their needs as fully as they now respond to other medical problems.
1. The cardiac and respiratory responses shown by muskrats in both unrestrained and restrained dives have been compared with responses elicited by stimulation of a number of cardio-depressant receptor inputs, in an attempt to determine which are most important in initiating and maintaining diving bradycardia. 2. In unrestrained voluntary dives heart rate fell from 310 +/- 3 to 54 +/- 3 beats min-1 in 1 to 2 sec, which was significantly below that seen in dives by restrained unanaesthetized or anaesthetized animals. 3. Pouring water on the external nares during maintained artificial ventilation caused heart rate to decline to 76 +/- 12 beats min-1 after 1 sec. Flowing water through the internal nares caused apnoea, in the expiratory position, and bradycardia within one third of a second. Heart rate fell to 20 +/- 2 beats min-1, 1 sec after the start of water flow. Substituting saline for water reduced both the apnoeic and cardiac responses. Bilateral section of the maxillary branch of V and the inferior laryngeal (X) nerves completely abolished the cardiac and respiratory response to water flow. 4. Artificial ventilation throughout periods of nasal stimulation with water or saline reduced the bradycardia, although even the saline driven response could not be completely abolished. Lung deafferentation eliminated any direct effect of artificial ventilation on heart rate during nasal stimulation. 5. Lung deflation caused bradycardia within 0.97 +/- 0.17 sec, heart rate falling from 268 +/- 7 to 59 +/- 4 beats min-1. Bradycardia also occurred during maintained lung inflation but it was delayed for a period which varied from 6.8 +/- 1.8 sec at an inflation pressure of 0.5 kPa to 35 +/- 7 sec at 1.5 kPa. 6. Bradycardia caused by nasal water flow or lung deflation was unaffected by bilateral section of the sinus nerve. 7. Artificial ventilation of paralysed muskrats with 5% CO2 in N2 caused bradycardia when Pa, O2 reached 8.4 +/- 0.8 kPa and heart rate declined to 76 +/- 7 beats min-1 at 4 kPa. Bilateral section of the sinus nerve delayed bradycardia until Pa, O2 reached 4.5 +/- 0.5 kPa. 8. These results suggest that the cardiac response to submergence could be the expression of input from three groups of receptors, nasal, lung and carotid chemoreceptors, although it is not clear how they interact with one another to generate the cardiac responses displayed by unrestrained animals during submergence.
1. Single nerve fibre discharge has been recorded from slowly adapting pulmonary stretch receptors in single-pithed turtles on artificial ventilation. 2. Receptor discharge during static and dynamic lung inflations showed that lung volume was the major stimulus of these receptors. The rate and degree of change in transpulmonary pressure were without direct effect. 3. The response of these receptors to static and dynamic lung inflation differed only quantitatively from those of bronchopulmonary stretch receptors in mammals. The lower discharge frequencies and sensitivities of the turtle receptors may arise from the low body temperature of these animals. 4. The sensitivity of turtle pulmonary receptors to CO2 was greater than that recorded for bronchopulmonary receptors of mammals although the effects of CO2 on receptor discharge were qualitatively similar. In several instances, receptor discharge was totally inhibited throughout the ventilatory cycle by inflation with 5--10% CO2 in air.
A method is described for measuring distribution of intrarenal blood flow in anesthetized rats by a xenon-133 washout technique that avoids the trauma of opening the abdominal cavity and manipulating the kidney. Precise delivery of the tracer to the kidney and fine collimation of the radiation reduces the amount of tracer required. Washout curve analysis is achieved by a multifit computer program that accepts only count rates and time as input data.